Biomedical Engineering Reference
In-Depth Information
rate of the loop's opening and closing is of order In contrast, NMR spectroscopy
experiments showed low order parameters for various NH groups (Kay et al., 1989;Kay
1998) NMR dynamics experiments indicated that residues in the adenosine binding
site of dihydrofolate reductase such as Lys 38, Val 88 of a hinge, and residues of the
and loops involve large-amlpitude motion on the fast time scale (Palmer et
al., 1996). These regions are implicated in the transition state stabilization and ligand-
dependent conformational changes.
According to experimental data on Mössbauer spectroscopy, at ambient temperatures
the myoglobin heme group exhibits the unharmonic nanosecond motion with
(Frolov et al., 1977; Belonogova et al., 1978; Parak et al., 1982). The flexibility of
the cavity of the myoglobin active site is evidenced by the mobility of a spin probe, a
derivative of isocyanate attached to the heme group in the single crystal. At room
temperature the mobility parameters were found as follows: correlation frequency
is
about
kcal/mole.,
(Likhtenshtein and Kotelnikov, 1983;
Likhtenshtein, 1988a).
The influence of solvent viscosity on the surface and the structural dynamics of the
heme group in the myoglobin active site was studied using the ultrafast infrared
vibrational echo method. (Rector et al. 2001) It was shown that pure dephasing of the A1
CO stretching mode of myoglobin-CO is markedly dampened in the presence of ethylene
glycol and trehalose and with a temperature increase. The authors concluded that when
the solvent viscosity and temperature are lowered, the increased rate of fluctuation of the
protein surface allows more rapid internal protein dynamics including the area of the
protein active site.
4.1.5. SIMULATION OF PROTEIN MOLECULAR DYNAMICS
Availability of supercomputers and development of elegant molecular methods of
dynamics simulation have been made a basis for the employment of explosive methods
and a wide range of successful applications (Karplus and Petsko, 1990). The computer
simulation produces individual particle motions as a function of time followed by the
examination of specific contributions to the process.
Dynamic simulation for a protein includes the following steps:
1) Establishment of potential energy functions for interaction between atoms. Usually
only empirical energy functions can be used for calculations for proteins. These
functions are generally composed of bonding terms representing bond length, bond
angles, torsional angles, Van der Waals interactions and electrostatic contributions.
2) A set of atomic coordinates is obtained from X-ray crystallographic or NMR
structure data, or by model building. The structure is first refined to relieve local stresses
due to overlaps of non-bonded atoms, bond-length and angles distortions, etc.
3) Using the classic Newton's law and are the force on the atom,
its mass, and its acceleration, respectively) and taking into consideration a Maxwellian
distribution for a given temperature, a simulation of the atoms velocities is performed for
a few picoseconds.
4) For relatively small proteins, like myoglobin, about 1,000 water molecules can be
included in the calculation. For large proteins, simplified treatments are used. A set of
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